Cyanoethylated products and preparation thereof



Patented Feb. 12, 1946 CYANOETHYLATED PRODUCTS AND PREPARATION THEREOF Herman A. Brnson, Philadelphia, Pa., assignor to The Itesinous Products & Chemical Company, Philadelphia, Pa., a corporation of Delaware No Drawing. Application March 2, 1943, Serial No. 477,763

6 Claims. ('01. 260-464) This invention relates to a method for the cyanoethylation of ketones having in juxtaposition to the ketonic carbonyl group a carbon atom hearing at least one reactive hydrogen atom and to the products thus obtained. More particularly, the present invention relates to the cyanoethylation of esters and substituted amides of a carboxylic acid which contains in a-position to the modified carboxylic acid group a CH: group activated by a radical which contains an atom having a multiple bond directly connected thereto,

- said atom being attached to said CH: group. Such s CH2 group is specifically foimd in functional derivatives of acetoacetic acid and, more particularly, the esters, amides, and nitriles thereof.

This application combines in part the disclosure act with acrylonitrile to form the dicyanoethylated product. Specifically, the final end products have the structures:

CHiCHsCN cnicoircoon' HsCHsCN and CHICHICN C ONHR" HICHICN wherein R and R" represent alkyl, aryl, arallrvl,

of application Serial No. 389,332, filed April 19,

1941, and in part the disclosure of application Serial No. 436,619, filed March 28, 1942.

According to this invention, acrylonitrile is reacted in the presence of an alkaline condensin agent with a ketone having an .active methyl,

methylene, or methenyl group immediately adja-' cent to its carbonyl group. By the reaction, a ,8- cyanoethyl radical is attached to the carbon atom adjacent to the carbonyl group. Ii more than one hydrogen is present on thi carbon atom, then more than one cyanoethyl group may be introduced.

In particular, one or two molecules of'acrylonitrile may be reacted in the presence of an alkaline condensing agent with a functional derivative of acetoacetic acid, such as an acetoacetic ester, nitrile or substituted amide, whereby one or two cyanoethylradicals become attached to the carbon atom which is in a-pOSitiOll to the modified carboxylic acid group of the acetoacetic chain. This reaction is conveniently represented as follows:

, CH CHgCN cmcocmn+cm==oncn cmco HR and 4 CHQCHQCN cmcocnm+zcm=cncn cmoo -11 1 meme:

wherein R represents a modified carboxylic acid group, particularly a carboxylic ester or carboxylic substituted amide radical. Obviously, the monosubstltuted monocyanoethylated product can reand cycloalkyl groups or such groups containing neutral substituents.

Among the alkaline condensing agents which have been found eii'ective for promoting the reaction are the oxides, hydroxides, hydrides, amides,

and alcoholates of the alkali metals or the alkali metals themselves. Similarly, the alkaline earth metals and their alkaline compounds may be used. There may also be used one of the strongly basic non-metallic hydroxides such as the quatemary ammonium hydroxides. Of these a particularly eflective product is the aqueous solution cfintaining 40% of trimethyl benzyl ammonium hydroxide which is available commercially under the trade name of Triton B. One or several oLthese materials are suspended or, preferably, dissolved in the ketone itself or in a solution of the ketone in an inert liquid, such as dloxane, ether, or benzene,

or in a liquid which is less reactive than the reacting ketone, such as water, or tertiary butyl alcohol.

The quantity of alkaline condensing agent re- I quired is relatively small, amount of the order of 1% to 10% on the combined weight of the reactants usually being'sufllcient. Since the condensation ceases if the alkali is depleted by side reactions or impurities of an acid nature in the. starting materials, it is advantageous to test the reaction mixture for alkalinity towards red litmus from time to time during the condensation and, ii an alkaline reaction is no longer shown, to add more alkali to make up for the loss. After the reaction is substantially complete, it is often desirable to neutralize the reaction mixture before the desired product is isolated. Thereactio'n is applicable to a wide variety or ketonesof the aliphatic, arylaliphatic, aromatic,

cycloaliphetic, and heterocyclic series, including ketones.

saturated or unsaturated mono-ketones or poly- The ketones may contain other functional groups than the carbonyl group so long as they do not readily destroythe alkaline condensing agent used. For example, these groups may be chloro, bromo, acyl, alkoxy, aryloxy, thioether, tert.-amino, sulfonyl, carbalkoxy, carbamyl, thiocyano, or cyano groups. The ketone ma contain more than one active methyl, methylene, or methenyl group.

Among the typical ketones having reactive groups suitable for the purpose of this invention may be mentioned the following: Acetone, phenoxyacetone, 'cyano-acetone,. ethoxy-acetone, acetophenone, p-methyl-acetophenone, N-methyltriacetonamine, acetyl-p-cymene, acetyl tetrahydronaphthalene, p-acetyl' diphenyl, acetyl anthracene, acetyl phenanthrene, p-methoxyacetophenone, p-chloro-acetophenone, p-bromoacetophenone, methyl-,B-naphthyl ketone, acetyl cyclohexane, cyclopentanone, cyclohexanone, m-, or p-methyl cyclohexanone, o-methallyl cyclohexanone, 0-, m-, or p-phenyl cyclohexanone, oor p-cyclohexyl-cyclohexanone, oor p-benzyl cyclohexanone, menthone, p-tert.-butyl cyclohexanone, p-tert.-amyl cyclohexanone, o-cyclohexylidene cyclohexanone, acetonyl acetone, diacetone alcohol, mesityl oxide, phorone, methyl ethyl ketone, methyl propyl ketone, methyl isobutyl ketone, di-isopropyl ketone, methyl-n-amyl ketone, dl-n-propyl ketone, methyl-n-hexyl ketone, 5-ethyl-nonanone 2, methyl heptadecyl ketone, propionhenone, butyrophenone, stearophenone, 1,8-dibenzoyl octane, 1,4-dibenzoyl butane, dibenzylketone, desoxybenzoin, benzal acetone, dibenzal acetone, a-tetralone, furfural acetone, furfural-acetophenone, acetophopanol, cholestanone, androsterone, acetoacetic ester, benzoyl acetic ester, acetoacetic amide, acetoacetic nitrile, acctoacetanilide, Z-acetothienone, and other aliphatic, aromatic, arylaliphatic, cycloaliphatic, and heterocyclic ketones having one or more reactive hydrogen atoms attached to a carbon atom contiguous to a C=O group.

Typical acetoacetic acid compounds which can be used are the methyl, ethyl, isopropyl, butyl, benzyl or cyclohexyl esters, the anilide, chloroanilide, ethyl amide, butylamide, laurylamide or cetyl amide, the chloro-aniiide and homologues thereof. The exact nature of the ester group or amide group is not a determining factor in this reaction, any ester or substituted amide group being permissible.

Depending upon the number of available hydrogen atoms in the reactive methyl, methylene, or methenyl groups contiguous to carbonyl in the ketones used, and upon the quantity of acrylonitrile employed, one or more d-cyanoethyl groups may be. introduced. The condensation takes place readily at temperatures from about 0 to about 80 0., although initial temperatures of 25 C. to 60 C. are.preferred. The reaction is usually exothermal so that cooling, at least during theiinitial part of the condensation, is generally advantageous in order to control the vigor of the reaction and to prevent undesired polymerization or side reactions. In this connection, it is sometimes desirable to add inhibitors such as hydroquinone, catechol, finely divided copper, copper compounds, or sulfur, etc.

In general, methyl ketones having the formula Mo -CH3, where R is aryl (as in acetophenone and its homologues) readily take up as many as three mols of acrylonitrile as follows:

CHaCE hCN RCOCHS+3CHQ=CHCN ncoccmcmcn CH'CHICN whereas cyclic ketones having the carbonyl between two -CHagroups, as in cyclopentanone, cyclohexanone, and their homologues, readily take up as many as four mols of acrylonitrile as follows:

Nccmcn, cmomoN Ncomc. crncmcx Where there is a choice between a methylene and a methyl group, as in methyl ethyl ketone and its homologues, the cyanoethyl radical appears to replace the hydrogen 0! the methylene group first. For example, methyl ethyl ketone, methyln-amyl ketone, methyl-n-hexyl ketone give crystalline di-cyanoethylation products which, however, do not readily show the iodoform test characteristic of COCH 1 groups. Ketones such as acetoacetic ester, amide, or nitrile readily take up two mols of acrylonitrile to di-cyanoethylate the CI-I2 group:

CHaCOCHzQOCICzHr-HZCHFCBCN CHzCHrCN cmoo 4000.11.

. HQCHICN Where one or more --CH groups are contiguous to carbonyl, each reactive hydrogen atom of the methenyl groups can be replaced by CH2-CHz-CN; for example, diisopropyl ketone yields I CH: CH:

cnood-c'mcnicn C 1 Hz and CH; CH:

rrcomcmd-cod-cmcmcrr Finally, unsaturated ketones, for example,

' mesityi oxide, take up two mols of acrylonitrile to form a di-cyanoethylated product. The product can be further cyanoethylated on its reactive methyl groups.

The fi-oyanoethylation products obtainable by the present process are new compounds. They are useful as intermediates for the preparation of monocarboxylic or polycarboxylic acids, amides, esters, amines, or polyamines, amidines, amino acids, amino alcohols, or thio-amides by the usual reactions characteristic of the nitrile group. Many of the compounds may find uses in diverse fields, including synthetic resins, artificial fibers, plastics, plasticizers, pharmaceuticals, insecticides, textile finishing and other commercial applications.

The following examples illustrate this invention, it being understood that, although trimethyl benzyl ammonium hydroxide is the preferred alkaline condensing agent, others, such as sodium ethylate, potassium tert.-amylate, sodium methsa le 1 (a) To a solution or 49 grams of cyclohexanone (0.5 mol) in 200 grams of benzene, there was added 5 grams of an aqueous 40%-solution oi trimethylbenzylammonium hydroxide. The mixture was stirred rapidly in a glass vessel fitted with a thermometer and reflux condenser, while methyl elclohexanone. It boiled between 275- I 108 grams of acrylonitrile (2 mols) was added dropwise during a two-hour period and while the. reaction mixture was maintained between 30 and 45 C. by means of external cooling. The

mixture was stirred for about four. hours longer until no more heat wasevolved. At the end oi this time, a thick magma of crystalline material hadformed. This was filtered oil sharply by suction, washed with a little methanol, and dried. There was obtained 139 grams of small, creamcolored crystals. The product can be recrystallized from acetone -in the form of colorless, fine needles, meltingwhen Pure at 165 0. Its analysis corresponds to tetra-(p-cyanoethyl) -cyclohexanone having the formula:

CHzCHzCN /C C-CHaCHzCN It is only slightly soluble in benzene or methanol. When boiled with aqueous 10% potassium hydroxide solution, th tetra-(p-cyanoethyl) -cyclohexanone is readily hydrolyzed to the. corresponding polycarboxylic acid which separated in the form of colorless crystals upon acidifying the NC CHsCH:

reaction mixture with hydrochloric acid. Upon recrystallization from hot water, itforms color: less needles melting at 179-180 C.

(b) By using only 53 grams of acrylonitrile (1 mol) in the above procedure, the yield of tetra- (p-cyanoethyl) -cyclohexanone fell to 57 grams.

' From the filtrate there were isolated two products, one a colorless oil boiling at 1509-160 C./l0

mm. consisting of mono-(,s-cyanoethyl) -cyclohexanone:

H: \G I v and the other a di-(c'yanoethyl) -cyc1ohexanone boiling at 197-207 C./1 mm., which crystallized from benzene in colorless needles melting when pure at 69.5 C.

In place of trimethyl benzyl ammonium hydroxide, one may use 2 grams of sodium methylateas'condensation catalyst.

In the same manner, 0-, m-, or p-alkyl-, aryl-, aralkyl-, cycloalkyl, or .cyano-cyclohexanones can be used in place of cyclohexanone itself.

(o) By adding 42.4 grams of acrylonitrile to a stirred solution of 2 grams of 40% potassium hydroxide solution, 50 grams of dioxane. and 19.6 grams of cyclohexanone at 40-45 C., therewas Emple 2 To a solution of 144 grams or methyl ethyl ketone (-2 mols) and 144 grams of benzene, there was added 10 grams of an aqueous 40% solution 01' trimethyl benzyl ammonium hydroxide. The mixture was stirred and cooled to 30-35 C. while 212 grams of acrylonitrile (4 mols) was added dropwise during two and one-half hours. After the addition, the mixture was stirred for three hours. There was then added 50 cc. of water and sumcient 10% hydrochloric acid to render the I solution slightly acidic. The benzene layer was separated, filtered from a small amount of polymer, and the benzene removed by evaporation.

The residual oil was then distilled under reduced pressure (1 mm). After a small i'orerun, the main fraction came over at 184-19 5 C./1 mm. as a pale'yellow oil weighing 177 grams. 0n

standing, it solidified to a crystalline mass which,

. Examples To a solution of 42 grams of cyclopentanone (0.5 mol) in 200 grams of benzene, there was added 5 grams of an aqueous 40% solution of trimethyl benzyl ammonium hydroxide. The mixture was stirred and cooled to 35-4,5 C. while 106 grams of acrylonitrile (2 mols) was added dropwise during one and one-half hours. Crystals began to separate within a few minutes after the addition was begun. As the reaction proceeded, itwas necessary to add 200 cc. oi benzene to prevent'clogging of the stirrer by the crystalline mush. The mixture was allowed to stand for eighteen hours before the crystals were filtered by suction.' The product can be recrystallized from hot methyl ethyl ketone or gly'col monoethyl ether (Cellosolye) from which it separates in colorless crystals melting, when pure, at 175 C. Its analysis corresponds to tetra-(fl-cyanoethyl) -cyclopentanone, having the formula:

NC CH:CH\: 5 CHzCHzCN NC smo cmcmcN CH:C1d: It is only very slightly soluble in benzene, toluene.

obtained 42 grams of tetra-(p-cyanoethyl) -cyclo-,

hexanone, having a melting point of 165 C.

(41) By adding63.5 grams of acrylonitrileto a stirred solution of 5 grams of aqueous 40% trimethyl benzyl ammonium hydroxide, 200 grams of benzene, and 44.8 grams of orthomethyl cyclohexanone at 30-40.C., there was obtained, after washing and drying, 103 grams 01 a syrup essentially of tri-(p-cyanoethyl) -o- .or dioxane. The yield was 144 grams, which corresponds to 97.3% of theory. 7 Example 4 212 grams of acrylonitrile was added dropwise during the course of two and one-half'hours to a stirred mixture of grams of'dioxane, 228 grams of methyl-n-amyl ketone, and 10 grams of aqueous 38% 'trimethyl benzyl ammonium hydroxide solution while the reaction mixture was maintained between 30 and 33 C. by external cooling. After the addition, the solution was stirred for twenty hours at room temperature. It was then acidifledwith dilute hydrochloric acid, taken up'in ethylene dichloride, and the solution washed thoroughly with water. The oil layer was evaporated to dryness under reduced pressure on a steambath. The residual oil, weighing 400 grams, was distilled in vacuo. After a small forerun of unchanged ketone, a fraction distilled over at 195-200 C./1-2 mm. as a colorless oil which solidified to a crystalline mass. The yield was 175 grams. Upon recrystallization from alcohol, it formed colorless crystals meltin at 63 C., the analysisof which corresponds to that for a di-(cyanoethyl)-heptanone. The residual pitch consisted of higher cyanoethylation products.

Example 5 To a solution of 128 grams of octanone-Z in 200 grams of benzene, there was added 5 grams of an aqueous 40% solution of trimethyl benzyl ammonium hydroxide. The mixture was stirred and cooled to 30-40 C. while 106 grams of acrylonitrile was added dropwise thereto during a twohour period. The mixture was stirred thereafter for one hour, then washed with water, followed by dilute hydrochloric acid, and then with water. The benzene layer was separated, filtered from a small amount of resin, and the filtrate evaporated under reduced pressure. The residual oil was distilled in high vacuo. The fraction boiling at 195-200 C./1 mm. formed a pale yellow oil which crystallized on cooling. After recrystallization from ethanol, it formed colorless Example 6 To a solution of 63 grams of p-a,a, ,y-tetramethylbutyl cyclohexanone (0.3 mol) in 100 grams of dioxane, there was added 3 grams of an aqueous 40% solution of trimethyl benzyl ammonium hydroxide. The mixture was stirred and cooled to 3040 C. while 63.6 grams of acrylonitrile (1.2 mols) was added dropwise thereto during one and one-quarter hours. The mixture was stirred for about one hour longer at room temperature (25-30 C.) and was then warmed to 43 C. for'two hours. It was cooled, acidified with dilute hydrochloric acid, and washed with water. The oil was then dried on a steam bath under reduced pressure. When cold, it formed a pasty crystalline mass weighing 118 grams. The product can be recrystallized from boiling methanol. It separates in colorless needles melting, when pure, at 155-156 C. Its

analysis corresponds to tetra-(B-cyanoethyl) tert.-octyl-cyclohexanone having the formula:

In the same manner, p-phenyl cyclohexanone, p-cyclohexyl-cyclohexanone, p-tert.-butyl-cyclohexanone, p-tert.-amyl-cyclohexanone, p-benzyloyclohexanone, or p-methyl-cyciohexanone can be used mol for mol inplace of thetert-octyicyclohexanone to yield the corresponding tetra-pcyanoethylation products thereof.

Example 7 To a solution or grams of acetophenone in 60 grams of dioxane containing 5 grams of aqueous 40% trimethyl benzyl ammonium hydroxide solution was added 79.5 grams of acrylonitrile dropwise during two hours, while the mixture was stirred and maintained between 30 and 40 C. by external cooling. During the addition, crystals began to separate. After the acrylonitrile had been added, the mixture was stirred one hour longer and filtered. Ther was obtained 79 gramsof pinkish crystals which, upon recrystallization from glycol monoethyl ether ("Cellosolve) formed colorless needles melting at 128- 129 0., the analysis or which indicated the compound to be tris-(p-cyanoethyDmethyl phenyl ketone having the formula:

crncmcN O0 o-e-cmcmcN dnioniou The original filtrate contains further quantities of the above compound, together with lower cyanoethylated material.

In place of acetophenone, one may use its nuclear substitution products, for example, its al-' kyl, aralkyl, aryl, cycloalkyl, alkoxy, aryloxy, halogen, or benzoyl derivatives, to obtain the corresponding tri-cyanoethylated products in the manner indicated above.

Example 8 To a solution of 34 grams of methyl-Z-naphthyl ketone in 100 cc. of dioxane and 2 grams of aqueous 38% trimethyl benzyl ammonium hydroxide solution, there was added dropwise 31.8 grams of acrylonitrile during thirty-five minutes, while the reaction mixture was stirred and maintained between 20 and 35 C. by means of external cooling. The mixture was then stirred four hours longer at room temperature. The dark solution was acidified with dilute hydrochloric acid, poured into two liters of water,v and the yellowish, viscous oil separated by taking it up in ethylene dichloride and washing the solution thoroughly with water. Upon evaporating away the ethylene dichloride under reduced pressure on a steam bath, there was obtained a reddish, viscous syrup weighing 64 grams. Upon the addition of 200 cc. of ethanol, the mixture crystallized. Aftture, it became crystalline,

er recrystallization from hot ethanol, the product separated in colorless large plates melting at 122 C. The compound contains three cyanoethyl radicals and has the formula:

' CHaCHzCN Example 9 The yield was 32 grams or white crystals. After recrystallization. from dioxane, tri-(p-cyanoethyl) -acetyl-diphenyl having the formula: v

- omcmcx mins...

HiCHiCN was obtained in the form of colorless plates Example 1!) CHaCHaCN co-c-cnl O monies To a solution consisting of 26.8 grams of propiophenone (0.2 mol), 50 grams or dioxane and 2 grams of aqueous 38% trimethyl benzyl ammonium hydroxide soluidon, there was added dropwise 21.2 grams of acrylonitrile (0.4 mol) during twenty minutes while the reaction mixture was stirred and maintained between 25 and 32 C.

by external cooling. The mixture was stirred for an additional five hours at 25C., then acidified with dilute hydrochloric acid, and poured into 300 cc. of water. The oil layer was separated, taken up in ethylene dichloride, washed thoroughly with,water, and the ethylene dichloride layer evaporated of! on a steam bath under reduced pressure. The residual oil weighed 48 grams. It was mixed with an equal weight of ethanol and chilled, whereupon the product crystallized. Aiter recrystallization from ethanol, the di-(p-cyanoethyli-propiophenone formed colorless crystals melting'at 66 C.

In place of propiophenone, its homologues, such asbutyrophenone, stearophenone, or its nuclear alkyl, aryl, aralkyl, cycloalkyl, nitro, halogen, alkoxy, or aryloxy derivatives may be used to obtain the corresponding di-cyanoethylated derivatives in the manner indicated above.

Example 11 Acrylonitrile (10.6 grams) was added dropwise during fifteen minutes to a stirred solution of 70 grams of dioxane, 16.1 grams or 1,8-dibenzoyloctane, and 2 grams of aqueous40% trimethyl benzyl ammonium hydroxide solution while the reaction mixture was maintained at 3'1-45 C. by external coolingr The mixture was then stirred four hours longer at 25-30 C. and then stirred with water containing sumcient hydrochlorid acid to neutralize the alkali. The oil was taken up in ethylene dichloride, the oil layer separated, washed, and concentrated under reduced pressure on a steam bath until all the solvent was removed. The residual oil, weighing 26 grams, was redissolved in benzene, filteredto remove traces of polymer, and the benzene removed by evaporation in vacuo at 80-90 C v The final product was a viscous, reddish oil.

Its analysis indicated that it consisted essentially of tetra-(cyanoethyl) -dibenzoyl. octane having the probable formula:

cmonlcn cmcmcN co-c-cnrcm-cm-cm-cnrcnr -co mcmcn memoir under reduced pressure.

Eran isle 12 (a) Two'grams of powdered sodium methylate was added to 58 grams or methyl acetoacetateat 50-60 C. The solution was cooled to 20 C. and stirred while 26.5 grams of -acrylonitrile was added dropwise during fifteen minutes at 379-40 0. while the mixture was 'cooled. The product was then stirred for two hours longer at 40 C. and allowed to stand eighteen hours at room tern-9 V perature. It was then poured into dilute .acid, the oil layer separated, dissolved in toluene,

filtered from a small amount of polymer, and the toluene filtrate washed, dried, and then distilled The fraction boiling at,141-145'C./7 mm. was a colorless oil having the formula:

CHaCHaCN (b) To a solution of 58 grams of methyl acetoacetate, 100 grams of dioxane and '7 grams of aqueous 40% trimethyl benzyl ammonium invdroxide solution, there was added dropwise 53 grams of acrylonitrile while the solution was stirred and cooled to -40 C. The mixture was stirred iorone-half hour longer at room temperature and the crystalline product which resulted was filtered oil. The yield was 54 grams. A rurther quantity was isolated by adding water to the filtrate. v

The substance formed colorless crystals melting at 154 C. after recrystallization from acetone. Its analysis corresponds to di-(s-cyanoethyD- acetoacetic methyl ester:

cmcmcN cmco-c iooenl mcmcN (c) By using 65 grams of ethyl acetoacetate in place of the methyl acetoacetate in the above example, the corresponding di-( 8-cyanoethyl)- acetoacetic ethyl ester separated as a crystalline mass when the reaction mixture was poured into one liter of ice water. After recrystallization from ethanol, the compound formed colorless crystals melting at 82 C. g

-In the same manner; other esters or acetoacetic acid may be used, for example, the isopropyl,

the butyl, the benzyl, phenyl or cyclohexyl esters.

Example 13 I (a) To a solution of 53.1 grams of acetoacetanilide in 100 gramsof dioxane containing 2 grams of aqueous trimethyl benzylammonium hydroxide solution, there was added dropwise 31.8 grams of acrylonitrile while the mixture was stirred and cooled to 30,-33 C. when the exothermal reaction was finished, the mixture was warmed for two and one-half hours at 0., then cooled, washed with water containing suflicient hydrochloric acid to neutralize the alkali, and finally thoroughly washed with water. The product separated as a heavy oil; which, after being dried on a steam bath under reduced pressure, form'eda pale amber-colored, resinous mass. It was dissolved in hot ethanol from which it slowly crystallized on standing. The colorless,

vpure crystals obtained after repeated recrystallization from ethanol melted at 82 C. Analysis indicated the presence of two cyanoethyl groups corresponding to the formula: g cmonlclv .cm eo- CONH 'HaCHaCN 1 despite the fact that acetoacetanilide itself melts at 85 C. A mixed melting point 01 the two compounds, however, shows a big depression. I

In the same manner, the ethylamide, butylamide, laurylamide or cetylamide of acetoacetic acid may be used in place of the anilide,--

(b) To a solution of 63.5 grams of orthochloro-aceto-acetoanilide, 100 grams of dioxane and 2 grams of aqueous 40 trimethyl benzy1 ammonium hydroxide solution, therewas added dropwise, while the solution was stirred at 30-36 0., 31.8 grams of acrylonitrile. The mixture was then heated at 4;0-50 C. for three hours. The clear solution obtained was acidified with dilute hydrochloric acid, poured into ethylene dichloride, and washed with water. The ethylene dichloride was then evaporated ofi, under reduced pressure, on a steam bath. There was obtained I 92 grams of a pale amber, resinous syrup which became crystalline when it was dissolved in ethanol and chilled. Upon recrystallization from ethanol, 66 grams of colorless crystals melting at 105 C. was obtained. Analysis indicated the presence of two cyanoethyl groups corresponding to the formula:

01 CHQCHaQN l cmoo-ir-ooNn memoir Despite the fact thatv ortho-chloro-acetoacetanilide itself melts at very nearly the same temperature, a mixed melting point of the two compounds shows a big depression.

A mixture consisting of 100 grams of dioxane, 3 grams of aqueous 38% trimethyl benzy1 ammonium hydroxide solution, and 73.8 grams of 2,5-dichloro-acetoacetanilide was stirred and warmed to 40 C. while 31.8 grams of acrylonitrile was gradually added. The mixture was heated for two and one-half hours at 40-45 0., then cooled, neutralized with dilute hydrochloric acid, taken up in ethylene dichloride, and washed with water. The ethylene dichloride layer was separated and evaporated to dryness in vacuo on a 45 steam bath. The residue, weighing 89 grams, was a-viscous, sticky balsam which did not readily crystallize. On standing in chilled ethanol solution for some time, it gradually solidified to a crystalline mass which, after several recrystallizations from. ethanol, formed colorlesscrystals melting at 121 0., containing by analysis two cyanoethyl radicals and having the formula:

CHCHQCN CHsC 0- CONH HrCHaCN Example 14 mol blue indicator with dilute hydrochloric acid, 70

and stirred with an equal volume of ethylene dichloride. The solution was then washed with water and the ethylene dichloride layer separated and evaporated to dryness under reduced pressure. The residue, consisting of a partially cryse asoaeec talline syrup, weighed 55 grams. It was stirred with a little methanol and the solids filtered oil. The yield was 20 grams. Upon recrystallization from methanol, the. product formed colorless crystals melting at 116-l17 C., the analysis of which corresponds to that of a di-cyanoethylation product having the formula C12H18N2O. The original filtrate contained a further quantity of the above crystals, together with a liquid monodroxide.

cyanoethylation product of mesityl oxide boiling at 110-115 C./2 mm,

Example 15 To a clear solution of 58 grams of acetone and '9 grams of aqueous 14% trimethyl benzy1 ammonium. hydroxide solution, 159 grams of acrylonitrile was addeddropwise while the solution was stirred and cooled to 30-37 C. After the solution had stood for eighteen hours at room temperature, the crystalline reaction product was filtered off. Upon recrystallization from glycol monomethyl ether, it formed colorless crystals (12 grams) melting at 154 C., the analysis of which agreed with a tri-(cyanoethyD-acetone. The filtrate, upon neutralization with dilute hydrochloric acid, washing with water, and concentration in vacuo on a steam bath, yielded 109 grams of a syrupy material, comprising higher cyanoalkylation products, which decomposes on distillation under reduced pressure.

Example 16 To a solution of 5'? grams of acetonyl acetone in 100 grams of benzene was added 5 grams of aqueous 40% trimethyl benzy1 ammonium hy- The solution was stirred and held at 30-35 C. by cooling while 106 grams of acrylonitrile was added dropwise during the course of one hour. The deep red-brown solution was 4ov stirred for twenty hours at the ordinary temperature and the crystalline product then filtered off by suction. After the crystals were washed with methanol to remove dark-colored impurities, the product (18 grams) was recrystallized from acetonyl acetone. It separated in colorless crystals, having a melting point of 180 C. and containing 16.45% nitrogen by analysis, apparently a tetra-(fi-cyanoethyl)-acetonyl acetone. The original filtrate contains a mixture of higher and lower cyanoethylation products. After being washed with water and dried, it forms a, dark resin.

Example 17 To a solution of 138 grams of phorone, 138 grams of dioxane, and 9 grams of aqueous 38% trimethyl benzy1 ammonium hydroxide solution,

there was addeddropwise during fifty minutes 53 grams of acrylonitrile while the reaction mixture was stirred and cooled at 31-35 C. The mixture was stirred thereafter for twenty hours, at 25 0., then acidified with dilute hydrochloric acid, taken up in ethylene dichloride, washed thoroughly with water, and the ethylene dichloride layer evaporated to dryness in vacuo on a steam bath. The residual oil, weighing 182 grams.

' 200 C./1 mm., weighing 14 grams, formed 'a-yellow oil analyzing for a dicyanoethylation product ing38grams.

I 8,894,962 01' phorone. The residuerwhich resisted high vacuum distillation. was a pitch-like mass weigh- Example 18 Acrylonitrile (21.2 grams) was added dropwise during forty minutes to a mixture of 21 grams sticky syrup weighing 42 grams. consisting essen-' tially ot'a tetra-cyanoethyiation soluble in methanol.

Example 19 To a solution of 30 grams or 'p-methoxyacetophenone, 50 grams of dioxane, and 2 grams of 38% trimethyl benzyl ammonium hydroxide, there was added dropwise with stirring 31.8 grams of acrylonitrile at a temperature of 35 C.

product. Itpwas After the mixture was stirred for several hours at 25C., dilute hydrochloric acid was added until the mixture was acid to litmus. The product was mixed with ethylene dichloride and then washed with water. The ethylene dichloride layer was evaporated to dryness under reduced pressure on a steam bath. The residual oil, weighing 56 grams, became crystalline when it was stirred with a little methanol. The product, after recrystallization from methanol, separated in colorless needles melting at 133 C. and having the formula:

omorncN CHaOOC O-(i-GHQCHQCN HICHICN In the same manner, the p-ethoxy, p-phenoxy, and p-benzyloxy derivatives may be prepared from the corresponding p-substituted acetophenones.

' Example 20 Acrylonitrile (31.8 grams) was added dropwise during the course of thirty minutes to a stirred solution consisting of 30.9 grams of p-ch1oro-- acetophenone, 50 gram of dioxane, and 2 grams oi. aqueous 38% trimethyl benzyl ammonium hydroxide while the reaction mixture was cooled to 32-37 C. The product began to crystallize out at the end of this time. After the mixture had stood for eighteen hours, it was neutralized with 7 stirred rapidly. The mixture was-then heated for six hours at C. The product was cooled,

neutralized with dilute hydrochloric acid, taken up in ethylene dichloride, and washed thoroughly with water. The ethylene dichloride layer was then separated and evaporated to dryness in vacuo on a steam bath. The residual oil weighed 25 grams. Upon distillation at 1' mm., a pale yel-' low oil came over at 170-175 6., containing 5.60% nitrogen by analysis and corresponding to the mono-cyanoethylation product having the formula;

cmcngcn olnr-co-cn-coo'clm Example 22 I To a solution consisting of 57 grams of di-isopropylketone, 60 grams of tertiary butanol, and

4 grams of aqueous 38% trimethyl benzyl ammonium hydroxide, there was added dropwise 53 grams of acrylonitrileduring one hour while the reaction mixture was stirred and the temperature maintained at 33-35, C. The mixture was stirred thereafter for two hours at 25 0., neutralized with dilute hydrochloric acid, taken up in anequal volume of ethylene dichloride, and washed with water. The ethylene dichloride layor was evaporated to dryness in vacuo On a steam bath. The residual oil weighed 95 grams. Upon distillation at 1 mm., it gave a fraction weighing 62 grams, boiling between 80 and 115 C. Upon refractionation in vacuo, this cut yielded 33 I A higher boiling fraction distilling at 165-170 dilute hydrochloric acid and the crystals filtered off. .The yield was 39 grams. Upon recrystallization from methanol, the product formed colorless stout needles melting at 14 1-142 C, and having the formula:

cmcmcN memoir The original filtrate, upon evaporation, yielded 25 grams of viscous oil containing lower cyanoethylated products.

Example 21 To a solution of 19.2grams of benzoylacetic ethyl ester, 50 grams of dioxane, and 2 grams of aqueous 38% trimethyl benzyl ammonium hydroxide, there was added dropwise 10.6 grams of acrylonitrile at 80-32 C. while the mixture was grams of monocyanoethyl-diisopropyl ketone as a. colorless oil boiling at 128 C./10 mmyhaving a nw=1.4428 and d25-=0.9247 and having the formula:

C./l mm. was also obtained as a'colorles oil corresponding to the di-cyanoethylation product.

- Example 23 i 21.2 grams of acrylonitrile was added dropwise during fifteen minutes to a stirred solution of 27 grams of p-bromo-acetophenone, 50 grams or (ii-- oxane, and 2 grams of aqueous 38% trimethyl benzyl ammonium hydroxide, while the reaction mixture was maintainedbetween 30 and 40 C.

The solution was then stirred for twenty-four hours at 25 C., acidified with dilute hydrochloric acid, mixed with 50 cc. of ethylene dichloride, and the crystals filtered oil. The yield was 23 grams. After recrystallization from ethanol, the product formed colorless needles melting at 151-' 152 C. and having the formula:

. CHgCHsCN V BOG o-i-cmcmon memoir More of the above product can be recovered from the filtrate by evaporation and trituration with ethanol.

Erample 24 31.8 grams of acrylonitriie was added dropwise during twenty-five minutes to a stirred solution consisting of 26.8 grams of p-methyl acetophenone, 50 grams of dioxane, and 2 grams of aqueous 38% trimethyl benzyl ammonium bydroxide at 33-"-37 C. After standing foriortyeight hours, the mixture was neutralized with dilute hydrochloric acid and the crystalline product filtered off. The-yield was 25 grams. After recrystallization from ethanol, the product formed colorless needles melting at 161-162'C. and having the formula:

cmcmoN CHr-O-C O-i-CHlCHION memos: The filtrate contains a further quantity or the product.

Example 25 gradually solidified to a waxy crystalline mass..

After recrystallization from ethanol, the product formed colorless crystals melting at 80 C. and having the formula:

0 g CHaCHaCN CCH:CH:CN

I claim: a

1. A process which comprises reacting in the presence of a strongly basic quaternary ammonium hydroxide acrylonitrile and an ester of acetoacetic acid.

2. A process which comprises reacting in the presence of trlmethyl benzyl' ammonium hydroxide acrylonitrile and an ester, of acetoacetic acid.

, 3.- A process which comprises reacting in the presence of a strongly basic quaternary ammonium hydroxide two molecular proportions of acrylonitrile and one molecular proportion of an ester of acetoacetic acid.

4. A process which comprises reacting in the presence of trimethyl benzyl ammonium hydroxide as a catalyst and dioxane as a solvent two molecular proportions of aorylonitrile and one molecular proportion of an ester of acetcacetlcac d.

5. A process which comprises reacting in the presence of a strongly basic quaternary ammonium hydroxide acryionitrile and ethyl acetoacetate. a

6. A process which comprises reacting in the presence of a strongly basic quaternary ammoniu'rnthydroxide acrylonitrile and methyl acetoace a e.

' A. eanson. 

